The Adenovirus Genome Contributes to the Structural Stability of the Virion

Saha, Bratati; Wong, Carmen; Parks, Robin J.

doi:10.3390/v6093563

Cited by 55 publications

(43 citation statements)

References 144 publications

(199 reference statements)

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“…It is possible that inactivation of E3 13.7K protein expression disrupts the stability of the hexon shell, leading to production of fragile capsids, which may be broken due to harsh treatment during CsCl/TEM procedures. Alternatively, it is possible that production of virions with fragile capsids could be due to the inefficient packaging of virion DNA (48). Several lines of evidence suggest that the capsid instability could be due to the loss of interaction of 13.7K with other adenovirus cement proteins.…”

Section: Discussionmentioning

confidence: 99%

Porcine Adenovirus Type 3 E3 Encodes a Structural Protein Essential for Capsid Stability and Production of Infectious Progeny Virions

Said

Woldemariam

Tikoo

2018

J Virol

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The adenovirus E3 region encodes proteins that are not essential for viral replication The porcine adenovirus type 3 (PAdV-3) E3 region encodes three proteins, including 13.7K. Here, we report that 13.7K is expressed as an early protein, which localizes to the nucleus of infected cells. The 13.7K protein is a structural protein, as it is incorporated in CsCl-purified virions. The 13.7K protein appears to be essential for PAdV-3 replication, as mutant PAV13.7 expressing a mutated 13.7K could be isolated only in VIDO AS2 cells expressing the 13.7K protein. Analysis of PAV13.7 suggested that even in the presence of reduced levels of some late viral proteins, there appeared to be no effect on virus assembly and production of mature virions. Further analysis of CsCl-purified PAV13.7 by transmission electron microscopy revealed the presence of disrupted/broken capsids, suggesting that inactivation of 13.7K protein expression may produce fragile capsids. Our results suggest that the PAdV-3 E3 region-encoded 13.7K protein is a capsid protein, which appears to be essential for the formation of stable capsids and production of infectious progeny virions. Although E3 region-encoded proteins are involved in the modulation of leukocyte functions (N. Arnberg, Proc Natl Acad Sci U S A 110:19976-19977, 2013) and inducing a lytic infection of lymphocytes (V. K. Murali, D. A. Ornelles, L. R. Gooding, H. T. Wilms, W. Huang, A. E. Tollefson, W. S. Wold, and C. Garnett-Benson, J Virol 88:903-912, 2014), none of the E3 proteins appear to be a component of virion capsid or required for replication of adenovirus. Here, we demonstrate that the 13.7K protein encoded by the E3 region of porcine adenovirus type 3 is a component of progeny virion capsids and appears to be essential for maintaining the integrity of virion capsid and production of infectious progeny virions. To our knowledge, this is the first report to suggest that an adenovirus E3-encoded protein is an essential structural protein.

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Section: Discussionmentioning

confidence: 99%

Porcine Adenovirus Type 3 E3 Encodes a Structural Protein Essential for Capsid Stability and Production of Infectious Progeny Virions

Said

Woldemariam

Tikoo

2018

J Virol

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“…This result indicates that the modularised genome of decompressed φX174 is having a negative effect on the thermal stability of the virion. This is not totally unexpected, as studies addressing heat stability of viral capsids with genomic variation have revealed different thermal stability between counterparts (Emerson, Arankalle et al, 2005, Ojosnegros, García-Arriaza et al, 2011, Saha, Wong et al, 2014. The physical properties of constituents within capsid shells (for example, salt ions and nucleotides) have been shown to directly influence a capsid's internal osmotic pressure, and consequently, mechanical stability (Evilevitch, Fang et al, 2008, Evilevitch, Lavelle et al, 2003, Ivanovska, Wuite et al, 2007, Roos, Bruinsma et al, 2010.…”

Section: Decompressed φX174 Virion Has Poor Heat Stability and Attachmentioning

confidence: 95%

Genome modularization reveals overlapped gene topology is necessary for efficient viral reproduction

Wright

Ruan

Molloy

et al. 2020

Preprint

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Sequence overlap between two genes is common across all genomes, with viruses having high proportions of these gene overlaps. The biological function and fitness effects of gene overlaps are not fully understood, and their effects on gene cluster and genome-level refactoring are unknown.The bacteriophage φX174 genome has ~26% of nucleotides involved in encoding more than one gene. In this study we use an engineered φX174 phage containing a genome with all gene overlaps removed, to show that gene overlap is critical to maintaining optimal viral fecundity. Through detailed phenotypic measurements we reveal that genome modularization in φX174 causes virion replication, stability, and attachment deficiencies. Quantitation of the complete phage proteome across an infection cycle reveals almost half the proteins display abnormal expression patterns.Taken together, we have for the first time comprehensively demonstrated that gene modularization severely perturbs the coordinated functioning of a bacteriophage replication cycle.This work highlights the biological importance of gene overlap in natural genomes and that reducing gene overlap disruption should be an integral part of future genome engineering projects.

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“…The first adenoviral genome to be sequenced was from subtype 2 (Ad2), composed of 35,937 base pairs (bp) [29]. Since then, the majority of subtypes have been sequenced and found to have similar genome organisation and functional gene products as Ad2, including Ad5.…”

Section: Structure Of Adenovirusesmentioning

confidence: 99%

Development of Oncolytic Adenoviruses for the Management of Prostate Cancer

Ali¹,

Halldén²

2018

Prostate Cancer

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Prostate cancer (PCa) is the fifth most common cause of cancer-related deaths in men globally. Androgen receptor (AR) signalling plays a vital role in initiation and progression and antiandrogens are standard of care first-line therapeutics. However, resistance frequently develops resulting in metastatic castration-resistant prostate cancer (mCRPC). Management of CRPC is currently chemotherapy and/or radiotherapy but is mostly palliative due to rapid development of resistance. The need for novel approaches to eliminate mCRPC is compelling; a promising option is replication-selective (oncolytic) adenoviruses with demonstrated efficacy in preclinical models of multidrug-resistant PCa. The safety of various viral mutants has been confirmed in numerous clinical trials with minimal toxicity in patients. Importantly, oncolytic adenoviruses synergise with the current standard of care for mCRPC even in treatment-resistant cells. In early phase I-II clinical trials, promising efficacy in patients with localised PCa was reported after intratumoural administration, and phase III trials are underway. To enable systemic delivery, for targeting of mCRPC, further developments are necessary because of the short half-life of the adenoviral mutants in human blood. Current progress in preventing the highaffinity binding of adenovirus to erythrocytes, hepatocyte uptake, and elimination by hepatic Kupffer cells will be described.

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The Adenovirus Genome Contributes to the Structural Stability of the Virion

Cited by 55 publications

References 144 publications

Porcine Adenovirus Type 3 E3 Encodes a Structural Protein Essential for Capsid Stability and Production of Infectious Progeny Virions

Porcine Adenovirus Type 3 E3 Encodes a Structural Protein Essential for Capsid Stability and Production of Infectious Progeny Virions

Genome modularization reveals overlapped gene topology is necessary for efficient viral reproduction

Development of Oncolytic Adenoviruses for the Management of Prostate Cancer

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